Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface

Autor(es)

Barbosa, Henrique ^[1] ; da Silva, Rafael Leonardo C. G. ^[2] ; Costa-Silva, Thais A. ^[1] ; Tempone, Andre G. ^[3] ; Antar, Guilherme M. ^[4] ; Lago, Joao Henrique G. ^[1] ; Caseli, Luciano ^[2]

Afiliação do(s) autor(es)

^[1] Fed Univ ABC, Ctr Nat & Human Sci, Santo Andre, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Chem, Diadema, SP - Brazil

^[3] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Inst Biosci, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOORGANIC CHEMISTRY; v. 101, AUG 2020.
• Citações Web of Science: 5

Resumo

In the present work, the oxoaporphine alkaloid dicentrinone was isolated, for the first time, from leaves of Ocotea puberula (Lauraceae). This alkaloid exhibited antiparasitic activity against trypomastigote forms of Trypanosoma cruzi (IC50 of 16.4 +/- 1.7 mu M), similar to the positive control benznidazole (IC50 of 18.7 +/- 4.1 mu M), reduced mammalian cytotoxicity (CC50 > 200 mu M), and a selectivity index (SI) higher than 12. These results were correlated with the effects observed using cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero- 3-phosphoethanolamine (DPPE), in Langmuir monolayers. Dicentrinone was incorporated in the films, sub-mitted to lateral compression, and characterized by tensiometry. As observed in compression-decompression and time-stability curves, dicentrinone expanded the lipid monolayers, decreased the compressional modulus of the film, and reduced the stability of the monolayer. Brewster Angle Microscopy and interfacial Infrared Spectroscopy showed that dicentrinone causes the monolayers to be segregated in phases, and to increase the number of gauche/trans conformers ratio for the lipid acyl methylene groups, indicating configurational disorder. As a result, dicentrinone caused a disturbance in the cell membrane models, altering the physicochemical properties of the lipid surface such as thermodynamic, rheological, morphological, and structural aspects. These results can be useful to understand the interactions between dicentrinone and lipid biological surfaces at the molecular level. (AU)

• Processo FAPESP: 18/00291-9 - Filmes de Langmuir e Langmuir-Blodgett de lipídios contendo fenilalanina desidrogenase para sensores de fenilalanina
• Beneficiário: Rafael Leonardo Cruz Gomes da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/10279-6 - Seleção e Otimização de Novos Candidatos a Fármacos para Leishmaniose e Doença de Chagas
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/03239-0 - Interfaces nanoestruturadas para a investigação de substâncias bioativas em modelos de membrana celular e para a construção de dispositivos optoeletrônicos enzimáticos
• Beneficiário: Luciano Caseli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07885-1 - Biomoléculas oriundas de espécies vegetais de áreas remanescentes da Mata Atlântica e do Cerrado para tratamento de doenças tropicais negligenciadas - aspectos químicos e farmacológicos
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular